UTX promotes CD8+ T cell-mediated antiviral defenses but reduces T cell durability
- Cell Rep. 2021 Apr 13;35(2):108966. doi: 10.1016/j.celrep.2021.108966.
- 1. Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Microbiology & Immunology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
- 2. Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
- 3. Adipocyte Biology and Gene Regulation Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
- 4. Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
- 5. Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
- 6. Department of Genetics, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Microbiology & Immunology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, UNC-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: [email protected].
Persistent virus infections can cause pathogenesis that is debilitating or lethal. During these infections, virus-specific T cells fail to protect due to weakened Antiviral activity or failure to persist. These outcomes are governed by histone modifications, although it is unknown which Enzymes contribute to T cell loss or impaired function over time. In this study, we show that T cell receptor-stimulated CD8+ T cells increase their expression of UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome) to enhance gene expression. During chronic lymphocytic choriomeningitis virus (LCMV) Infection in mice, UTX binds to enhancers and transcription start sites of effector genes, allowing for improved cytotoxic T lymphocyte (CTL)-mediated protection, independent of its trimethylation of histone 3 lysine 27 (H3K27me3) demethylase activity. UTX also limits the frequency and durability of virus-specific CD8+ T cells, which correspond to increased expression of inhibitory receptors. Thus, UTX guides gene expression patterns in CD8+ T cells, advancing early Antiviral defenses while reducing the longevity of CD8+ T cell responses.